Nzeera Ketter

• Group Leader at Johnson & Johnson

Background Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) reported in patients with mild-to-moderate Alzheimer’s disease in bapineuzumab phase III studies. Objectives Assess symptoms, clinical severity, and ARIA-E outcomes, and to evaluate effects on cognition and function. Methods A centralized systematic sequential locked...

Background A 3-year extension of two Phase III parent studies of intravenous (IV) bapineuzumab in patients with mild-to-moderate Alzheimer’s disease dementia (apolipoprotein (APOE) ɛ4 carriers and noncarriers) is summarized. Objectives The primary and secondary objectives were to evaluate the long-term safety, tolerability, and maintenance of effi...

Objective: To evaluate whether amyloid-related imaging abnormalities with edema/effusion (ARIA-E) observed in bapineuzumab clinical trials was associated with specific biomarker patterns. Methods: Bapineuzumab, an anti-β-amyloid monoclonal antibody, was evaluated in patients with mild to moderate Alzheimer disease. Amyloid PET imaging, CSF bioma...

Background: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). Objectives: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer’s disease randomized to bapineuz...

Objectives: Long-term safety and tolerability of ACC-001 (vanutide cridificar), an anti-amyloid-beta therapeutic vaccine, was evaluated in subjects with mild to moderate Alzheimer's disease. Design: Phase 2a extension studies of randomized parent trials were conducted in the United States, European Union, and Japan. Methods: Four immunizations...

Vanutide cridificar (ACC-001), an immunotherapeutic vaccine, is a potentially disease-modifying therapy that aims to reduce brain amyloid-β (Aβ) plaques in patients with Alzheimer's disease (AD). ACC-001 was evaluated in two phase 2a, multicenter, randomized, third party-unblinded, placebo-controlled, multiple ascending-dose studies of ACC-001 (3μg...

Background: ACC-001 is an investigational therapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease. Objectives: To evaluate safety, immunogenicity, impact on brain amyloid, and other exploratory endpoints in participants r...

Background: Vanutide Cridificar (ACC-001), a novel investigational immunotherapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease (AD). Objectives: To evaluate the immunogenicity, safety and impact of ACC-001 with Quillaja...

Background Amyloid-related imaging abnormalities due to haemosiderin deposition (ARIA-H) occur in patients with mild to moderate dementia due to Alzheimer's disease (AD) and have been reported with increased incidence in clinical trials of amyloid-lowering therapies under development for AD. Objective Our objective was to explore the relationship b...

Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease. We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the...

Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, pha...

Purpose: Effective treatment options for infections caused by P. aeruginosa and A. baumannii are limited. A promising alternative to current agents could be doripenem (DOR), a new carbapenem approved for the treatment of adults with complicated intra-abdominal (cIAI) and urinary tract infections (cUTI) in the United States, and cIAI, cUTI, and noso...

Background: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Afric...

The seizure-inducing potential of carbapenems has been debated since the introduction of imipenem/cilastatin over 20 years ago. Doripenem is a new carbapenem, recently approved in the US for the treatment of adults with complicated urinary tract infections (cUTI) or complicated intra-abdominal infections (cIAI), and additionally in the EU for nosoc...

Doripenem is a new carbapenem that has broad-spectrum activity against bacterial pathogens commonly responsible for nosocomial pneumonia (NP). It has several advantages over currently available carbapenems and other classes of drugs used in this indication. This prospective, randomized, open-label, multicenter study was designed to establish whethe...

Ventilator-associated pneumonia (VAP) is a common nosocomial infection that is associated with prolonged length of stay (LOS) and significant mortality. The aim of this study was to compare resource utilization with doripenem, an investigational carbapenem, versus imipenem from a hospital perspective among patients with VAP. This analysis was based...

Background: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial...

The identification of populations at risk of HIV infection is a priority for trials of preventive technologies, including HIV vaccines. To quantify incidence traditionally requires laborious and expensive prospective studies. The BED IgG-Capture enzyme immunoassay (EIA) was developed to estimate HIV-1 incidence using cross-sectional data by measuri...

Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conse...

The potential role of human immunodeficiency virus type 1 (HIV-1)—specific immune responses in controlling viral replication in vivo has stimulatedinterest in enhancing virus-specificimmunity by vaccinating infected individuals with HIV-1 or its components. These studies were undertaken to define patient populations most likely to respond to vaccin...

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk act...

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target tr...

Objective: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp12...

To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third var...

The NIAID-sponsored AIDS Vaccine Evaluation Group was established in 1988 to perform phase I/II clinical trials with candidate preventive HIV-1 vaccines. This report includes safety data from 1398 HIV-negative, healthy volunteers who were enrolled into 25 phase I and 1 phase H multicentered, randomized, double-blind studies evaluating seven recombi...

The potential role of T cells in the control of human papillomavirus type 6 (HPV-6) infections is an appealing premise, but their actual role has been sparsely investigated. Since HPV-6 infections are confined to the epithelium, such an investigation should focus on the T cells present at the site of infection (i.e., the warts). Therefore, we isola...

In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for o...

F105 is a human monoclonal antibody that binds to the CD4 binding site of human immunodeficiency virus type 1 gp120 and neutralizes clinical and laboratory isolates of the human immunodeficiency virus. This phase I study investigated the disposition of the antibody in humans. F105 was administered over a 60-minute period at two dose levels, 100 and...

A phase I double-blind trial was done to examine the safety and immunogenicity of a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1MN) third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected healthy adult volunteers. Subjects were randomly assigned to receive 20, 100, or 500 micrograms of vaccine or a...

A phase I double-blind trial was done to examine the safety and immunogenicity of a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1MN) third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected healthy adult volunteers. Subjects were randomly assigned to receive 20, 100, or 500 µg of vaccine or alum adju...

Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens. We performed a phase I trial of the safety and imm...